In vivo expression of a new hepatitis B virus protein encoded by a spliced RNA
Patrick Soussan, … , Christian Brechot, Dina Kremsdorf
Patrick Soussan, … , Christian Brechot, Dina Kremsdorf
Published January 1, 2000
Citation Information: J Clin Invest. 2000;105(1):55-60. https://doi.org/10.1172/JCI8098.
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Article

In vivo expression of a new hepatitis B virus protein encoded by a spliced RNA

Abstract

Hepatitis B virus (HBV) is a small DNA virus with a compact genomic organization. All HBV proteins identified to date have been encoded by unspliced HBV RNAs. Spliced HBV RNAs have been described, but their functions are unknown. We show here that a singly spliced HBV RNA encodes a novel HBV protein in vivo. This HBV splice-generated protein (HBSP) corresponds to the fusion of a part of the viral polymerase and a new open reading frame that is created by the splicing event. In vivo, HBSP protein was found in HBV-infected liver samples, and anti-HBSP antibodies occurred in one-third of sera samples collected from chronic HBV carriers. In vitro, the ectopic expression of HBSP had no effect on viral DNA replication or transcription but induced cell apoptosis without a cell-cycle block. Overall, our results suggest that HBV has evolved a mechanism that directly modulates virus-cell interaction through RNA splicing.

Authors

Patrick Soussan, Florianne Garreau, Hervé Zylberberg, Cyrille Ferray, Christian Brechot, Dina Kremsdorf

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Figure 1

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(a) Schematic representation of singly spliced HBV RNA and HBSP translat...
(a) Schematic representation of singly spliced HBV RNA and HBSP translation product. (b) Top: Indirect ELISA for the detection of anti-HBSP antibodies in sera from chronic HBV carriers (n = 45), in normal serum controls (NS, n = 45), and in sera from patients with HCV (n = 45), autoimmune hepatitis (AIH, n = 17), and chronic alcoholic cirrhosis (AC, n = 25). Bottom: Box plot representation of ELISA data. (c) Western blot analysis of liver biopsies. Top: HBSP was detected (using polyclonal chicken anti-HBSP antibodies raised against HBSP bacterial recombinant protein) in 4 HBV-infected livers (lanes 3–6), 2 HCV-infected livers (lanes 2 and 7), and 1 normal liver (lane 1). Middle: HBV envelope (HBsAg) and capsid (HBcAg) detection in the same samples using polyclonal HBs and HBc antibodies. Bottom: HBSP detection, without (left) or with (right) adsorption of anti-HBSP with GST-HBSP bacterial protein, in CCL13 GFP-HBSP–transfected cells (lanes 1 and 1′), HBV-infected livers (lanes 2, 2′, 3, and 3′), and normal liver (lanes 4 and 4′).